First-in-human Study of DRP-104 (Sirpiglenastat) as Single Agent and in Combination With Atezolizumab in Patients With Advanced Solid Tumors.

  • STATUS
    Recruiting
  • End date
    Dec 28, 2023
  • participants needed
    246
  • sponsor
    Dracen Pharmaceuticals, Inc.
Updated on 28 June 2021
cancer
cavities
carcinoma
warfarin
squamous cell carcinoma
lung cancer
metastasis
neutrophil count
chemotherapy regimen
pd-l1
cancer treatment
solid tumour
caries
atezolizumab
stage iv non-small cell lung cancer
platinum doublet
head and neck carcinoma
metastatic squamous cell carcinoma
advanced squamous cell carcinoma

Summary

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 (sirpiglenastat) administered via intravenous infusion or via subcutaneous injection as a single agent and in combination with atezolizumab in patients with advanced solid tumors and to assess preliminary safety and efficacy of which route of administration (intravenous or subcutaneous) will be selected for further development for the other two expansions of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations, and advanced squamous cell carcinoma of the head and neck (SCCHN).

Description

This study will be conducted in 4 Parts:

Part 1: Phase 1 single-agent dose escalation of DRP-104 (sirpiglenastat) in patients with advanced solid tumors to define the MTD (up to approximately 50 patients for each intravenous and subcutaneous cohort)

Part 2, Once the MTD of DRP-104 for the IV and subQ route of administration will be determined in Part 1, Part 2 will include 2 specific cohorts: Cohort 2 and 3 with one only selected formulation. Once the MTD of DRP-104 has been declared for either the IV or suQ cohort, Cohort 1 of Part 2 will separately expand for each cohort. -Cohort 1: Phase 1 single-agent safety expansion at the of DRP-104 in patients with advanced solid tumors (N= minimum of 14 and up to 20 patients for each intravenous and subcutaneous cohorts); The Sponsor will determine at completion of Phase 1 which route of administration will be further developed and continued for all subsequent Cohorts 2 and 3 and Parts 3 and Part 4 in combination with atezolizumab.

  • Cohort 2: Phase 2a expansion at the of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a KEAP1 mutation, NFE2L2 mutation and/or STK11 mutation (N=55 patients)
  • Cohort 3: Phase 2a expansion at the MTD of DRP-104 in recurrent, unresectable or metastatic SCCHN (N=15-25 patients).

Part 3: Phase 1 combination dose escalation of DRP-104 (sirpiglenastat) (with either IV or subcutaneous formulation selected) and atezolizumab in patients with advanced solid tumors previously treated with an anti-PD-1, anti PD-L1, and/or anti-CTLA-4 antibody, starting one dose level below the MTD of single-agent DRP-104 and in combination with atezolizumab (up to approximately N=12 patients).

Part 4: Phase 1 combination safety expansion at the MTD of DRP-104 (with either IV or subcutaneous formulation selected)with atezolizumab in a similar patient population as the dose-escalation (N=14 patients).

Details
Condition Recurrent NSCLC, Squamous Cell Carcinoma of Head and Neck, Squamous Cell Carcinoma of the Head and Neck, Squamous cell carcinoma, Non Small Cell Lung Cancer Metastatic, Squamous Cell Carcinoma, Advanced Solid Tumor, Recurrent Non-small Cell Lung Cancer, Advanced Malignant Solid Tumor, head and neck cancer, Non Small Cell Lung Cancer Recurrent, Head and Neck Cancer
Treatment Atezolizumab, DRP-104
Clinical Study IdentifierNCT04471415
SponsorDracen Pharmaceuticals, Inc.
Last Modified on28 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of advanced or recurrent, histologically or cytologically confirmed, measurable by RECIST 1.1 metastatic or unresectable solid tumor
Patient must have progressed on, be intolerant of, decline, or be ineligible for, all available standard of care therapies
Part 2: locally advanced or metastatic NSCLC with KEAP1, NFE2L2 and/or STK11 mutation ; Patients must have received at least a platinum doublet chemotherapy and an anti-PD-(L)1 antibody; Received up to 3 lines of systemic anticancer therapy in the recurrent or metastatic setting
Part 2: Recurrent, unresectable or metastatic squamous cell carcinoma of the head and neck (SCCHN) (oropharynx, oral cavity, hypopharynx or larynx); Patient must have received platinum containing chemotherapy and antiPD-(L)1 antibody in recurrent or metastatic setting
Part 3 and 4 - DRP-104 + atezolizumab Prior exposure to any checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PDL2, and/or anti-CTLA-4 antibody)
ECOG performance 0 or 1
Patient must consent to allow acquisition of existing FFPE tumor tissue; If unavailable, patient must consent to new pre-treatment tumor biopsy
All SCCHN patient, all NSCLC patients and all patients treated with combination of DRP-104 and atezolizumab will be required to undergo pre-treatment and post-treatment core or excisional biopsies
Pre-treatment and post-treatment core or excisional biopsies are optional for all remaining patients
Adequate baseline organ function as defined by: Absolute neutrophil count 1.5 109/L (1500/L); Hemoglobin 9 g/dL ;Platelets 75 109/L (75,000/L); Hepatic Total bilirubin 1.5 upper limit of normal (ULN): PT/INR and PTT 1.5 ULN, unless treated with warfarin; AST(SGOT)/ALT(SGPT) 3 ULN or 5 ULN for patients with liver metastases; Creatinine clearance 60 ml/min/1.73m2 measured or calculated
Cardiac QTc (Fridericia) <470 ms
Women of child-bearing potential and men who are sexually active must agree to use one highly effective method of contraception

Exclusion Criteria

Patients with primary central nervous system tumors and hepatocellular carcinoma
Patients with progressive or symptomatic brain metastases
Leptomeningeal disease
Spinal cord compression not definitively treated with surgery and/or radiation
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
Prior glutaminase inhibitor use
Prior systemic anticancer treatment (i.e. chemotherapy, biologic therapy, monoclonal antibodies, investigational agents) within 21 days or 5 half-lives, whichever is shorter
Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks prior to enrollment
Prior small port palliative radiotherapy within 14 days of start of Cycle 1
Any major surgery within 21 days from start of Cycle 1
Secondary malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
Has a known history of HIV, or HBV
Gastrointestinal (GI) function impairment or GI disease
Significant, uncontrolled heart disease and/or cardiac repolarization abnormality
Exclusion specific to only Part 3 and 4 (DRP-104 combined with atezolizumab): History of severe allergic, anaphylactic to chimeric or humanized antibodies or fusion proteins; Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells; Prior anti-PD-1, anti-PD-L1 and/or anti CTLA4- agent, patient must not have had a serious (> Grade 3) immune-related AE requiring treatment; History of autoimmune disease except hypothyroidism on thyroid replacement hormone therapy; History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis; Patients with underlying condition requiring systemic corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications or other systemic immunosuppressant medications may be enrolled in the study after approval by the Medical Monitor; Evidence or history of active or latent tuberculosis infection; Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
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